Tie2 as a novel key factor of microangiopathy in systemic sclerosis
Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Falk Moritz [verfasserIn] |
|---|
| Format: |
Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2017 |
|---|
| Schlagwörter: |
|---|
| Übergeordnetes Werk: |
Enthalten in: Arthritis research & therapy - London : BioMed Central, 2003, 19(2017) |
|---|---|
| Übergeordnetes Werk: |
volume:19 ; year:2017 |
| Links: |
|---|
| DOI / URN: |
10.1186/s13075-017-1304-2 |
|---|
| Katalog-ID: |
OLC1995453560 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | OLC1995453560 | ||
| 003 | DE-627 | ||
| 005 | 20230515114337.0 | ||
| 007 | tu | ||
| 008 | 170721s2017 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s13075-017-1304-2 |2 doi | |
| 028 | 5 | 2 | |a PQ20170901 |
| 035 | |a (DE-627)OLC1995453560 | ||
| 035 | |a (DE-599)GBVOLC1995453560 | ||
| 035 | |a (PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93 | ||
| 035 | |a (KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q DNB |
| 100 | 0 | |a Falk Moritz |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tie2 as a novel key factor of microangiopathy in systemic sclerosis |
| 264 | 1 | |c 2017 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 520 | |a Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. | ||
| 650 | 4 | |a Vascular endothelial growth factor | |
| 650 | 4 | |a Rodents | |
| 650 | 4 | |a Extracellular matrix | |
| 650 | 4 | |a Arthritis | |
| 650 | 4 | |a Hypoxia | |
| 700 | 0 | |a Janine Schniering |4 oth | |
| 700 | 0 | |a Jorg H W Distler |4 oth | |
| 700 | 0 | |a Renate E Gay |4 oth | |
| 700 | 0 | |a Steffen Gay |4 oth | |
| 700 | 0 | |a Oliver Distler |4 oth | |
| 700 | 0 | |a Britta Maurer |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Arthritis research & therapy |d London : BioMed Central, 2003 |g 19(2017) |w (DE-627)363765530 |w (DE-600)2107602-9 |w (DE-576)379407604 |x 1478-6354 |7 nnns |
| 773 | 1 | 8 | |g volume:19 |g year:2017 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1186/s13075-017-1304-2 |3 Volltext |
| 856 | 4 | 2 | |u https://search.proquest.com/docview/1906361809 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a SSG-OLC-NED | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 951 | |a AR | ||
| 952 | |d 19 |j 2017 | ||
| author_variant |
f m fm |
|---|---|
| matchkey_str |
article:14786354:2017----::i2snvlefcoomconiptyny |
| hierarchy_sort_str |
2017 |
| publishDate |
2017 |
| allfields |
10.1186/s13075-017-1304-2 doi PQ20170901 (DE-627)OLC1995453560 (DE-599)GBVOLC1995453560 (PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93 (KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc DE-627 ger DE-627 rakwb eng 610 DNB Falk Moritz verfasserin aut Tie2 as a novel key factor of microangiopathy in systemic sclerosis 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. Vascular endothelial growth factor Rodents Extracellular matrix Arthritis Hypoxia Janine Schniering oth Jorg H W Distler oth Renate E Gay oth Steffen Gay oth Oliver Distler oth Britta Maurer oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 19(2017) (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:19 year:2017 http://dx.doi.org/10.1186/s13075-017-1304-2 Volltext https://search.proquest.com/docview/1906361809 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 19 2017 |
| spelling |
10.1186/s13075-017-1304-2 doi PQ20170901 (DE-627)OLC1995453560 (DE-599)GBVOLC1995453560 (PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93 (KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc DE-627 ger DE-627 rakwb eng 610 DNB Falk Moritz verfasserin aut Tie2 as a novel key factor of microangiopathy in systemic sclerosis 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. Vascular endothelial growth factor Rodents Extracellular matrix Arthritis Hypoxia Janine Schniering oth Jorg H W Distler oth Renate E Gay oth Steffen Gay oth Oliver Distler oth Britta Maurer oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 19(2017) (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:19 year:2017 http://dx.doi.org/10.1186/s13075-017-1304-2 Volltext https://search.proquest.com/docview/1906361809 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 19 2017 |
| allfields_unstemmed |
10.1186/s13075-017-1304-2 doi PQ20170901 (DE-627)OLC1995453560 (DE-599)GBVOLC1995453560 (PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93 (KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc DE-627 ger DE-627 rakwb eng 610 DNB Falk Moritz verfasserin aut Tie2 as a novel key factor of microangiopathy in systemic sclerosis 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. Vascular endothelial growth factor Rodents Extracellular matrix Arthritis Hypoxia Janine Schniering oth Jorg H W Distler oth Renate E Gay oth Steffen Gay oth Oliver Distler oth Britta Maurer oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 19(2017) (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:19 year:2017 http://dx.doi.org/10.1186/s13075-017-1304-2 Volltext https://search.proquest.com/docview/1906361809 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 19 2017 |
| allfieldsGer |
10.1186/s13075-017-1304-2 doi PQ20170901 (DE-627)OLC1995453560 (DE-599)GBVOLC1995453560 (PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93 (KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc DE-627 ger DE-627 rakwb eng 610 DNB Falk Moritz verfasserin aut Tie2 as a novel key factor of microangiopathy in systemic sclerosis 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. Vascular endothelial growth factor Rodents Extracellular matrix Arthritis Hypoxia Janine Schniering oth Jorg H W Distler oth Renate E Gay oth Steffen Gay oth Oliver Distler oth Britta Maurer oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 19(2017) (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:19 year:2017 http://dx.doi.org/10.1186/s13075-017-1304-2 Volltext https://search.proquest.com/docview/1906361809 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 19 2017 |
| allfieldsSound |
10.1186/s13075-017-1304-2 doi PQ20170901 (DE-627)OLC1995453560 (DE-599)GBVOLC1995453560 (PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93 (KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc DE-627 ger DE-627 rakwb eng 610 DNB Falk Moritz verfasserin aut Tie2 as a novel key factor of microangiopathy in systemic sclerosis 2017 Text txt rdacontent ohne Hilfsmittel zu benutzen n rdamedia Band nc rdacarrier Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. Vascular endothelial growth factor Rodents Extracellular matrix Arthritis Hypoxia Janine Schniering oth Jorg H W Distler oth Renate E Gay oth Steffen Gay oth Oliver Distler oth Britta Maurer oth Enthalten in Arthritis research & therapy London : BioMed Central, 2003 19(2017) (DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 1478-6354 nnns volume:19 year:2017 http://dx.doi.org/10.1186/s13075-017-1304-2 Volltext https://search.proquest.com/docview/1906361809 GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 AR 19 2017 |
| language |
English |
| source |
Enthalten in Arthritis research & therapy 19(2017) volume:19 year:2017 |
| sourceStr |
Enthalten in Arthritis research & therapy 19(2017) volume:19 year:2017 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Vascular endothelial growth factor Rodents Extracellular matrix Arthritis Hypoxia |
| dewey-raw |
610 |
| isfreeaccess_bool |
false |
| container_title |
Arthritis research & therapy |
| authorswithroles_txt_mv |
Falk Moritz @@aut@@ Janine Schniering @@oth@@ Jorg H W Distler @@oth@@ Renate E Gay @@oth@@ Steffen Gay @@oth@@ Oliver Distler @@oth@@ Britta Maurer @@oth@@ |
| publishDateDaySort_date |
2017-01-01T00:00:00Z |
| hierarchy_top_id |
363765530 |
| dewey-sort |
3610 |
| id |
OLC1995453560 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1995453560</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230515114337.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">170721s2017 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13075-017-1304-2</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20170901</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1995453560</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1995453560</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Falk Moritz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Tie2 as a novel key factor of microangiopathy in systemic sclerosis</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Vascular endothelial growth factor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rodents</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Extracellular matrix</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Arthritis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hypoxia</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Janine Schniering</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jorg H W Distler</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Renate E Gay</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Steffen Gay</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Oliver Distler</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Britta Maurer</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Arthritis research & therapy</subfield><subfield code="d">London : BioMed Central, 2003</subfield><subfield code="g">19(2017)</subfield><subfield code="w">(DE-627)363765530</subfield><subfield code="w">(DE-600)2107602-9</subfield><subfield code="w">(DE-576)379407604</subfield><subfield code="x">1478-6354</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:19</subfield><subfield code="g">year:2017</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1186/s13075-017-1304-2</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://search.proquest.com/docview/1906361809</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-NED</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">19</subfield><subfield code="j">2017</subfield></datafield></record></collection>
|
| author |
Falk Moritz |
| spellingShingle |
Falk Moritz ddc 610 misc Vascular endothelial growth factor misc Rodents misc Extracellular matrix misc Arthritis misc Hypoxia Tie2 as a novel key factor of microangiopathy in systemic sclerosis |
| authorStr |
Falk Moritz |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)363765530 |
| format |
Article |
| dewey-ones |
610 - Medicine & health |
| delete_txt_mv |
keep |
| author_role |
aut |
| collection |
OLC |
| remote_str |
false |
| illustrated |
Not Illustrated |
| issn |
1478-6354 |
| topic_title |
610 DNB Tie2 as a novel key factor of microangiopathy in systemic sclerosis Vascular endothelial growth factor Rodents Extracellular matrix Arthritis Hypoxia |
| topic |
ddc 610 misc Vascular endothelial growth factor misc Rodents misc Extracellular matrix misc Arthritis misc Hypoxia |
| topic_unstemmed |
ddc 610 misc Vascular endothelial growth factor misc Rodents misc Extracellular matrix misc Arthritis misc Hypoxia |
| topic_browse |
ddc 610 misc Vascular endothelial growth factor misc Rodents misc Extracellular matrix misc Arthritis misc Hypoxia |
| format_facet |
Aufsätze Gedruckte Aufsätze |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
nc |
| author2_variant |
j s js j h w d jhwd r e g reg s g sg o d od b m bm |
| hierarchy_parent_title |
Arthritis research & therapy |
| hierarchy_parent_id |
363765530 |
| dewey-tens |
610 - Medicine & health |
| hierarchy_top_title |
Arthritis research & therapy |
| isfreeaccess_txt |
false |
| familylinks_str_mv |
(DE-627)363765530 (DE-600)2107602-9 (DE-576)379407604 |
| title |
Tie2 as a novel key factor of microangiopathy in systemic sclerosis |
| ctrlnum |
(DE-627)OLC1995453560 (DE-599)GBVOLC1995453560 (PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93 (KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc |
| title_full |
Tie2 as a novel key factor of microangiopathy in systemic sclerosis |
| author_sort |
Falk Moritz |
| journal |
Arthritis research & therapy |
| journalStr |
Arthritis research & therapy |
| lang_code |
eng |
| isOA_bool |
false |
| dewey-hundreds |
600 - Technology |
| recordtype |
marc |
| publishDateSort |
2017 |
| contenttype_str_mv |
txt |
| author_browse |
Falk Moritz |
| container_volume |
19 |
| class |
610 DNB |
| format_se |
Aufsätze |
| author-letter |
Falk Moritz |
| doi_str_mv |
10.1186/s13075-017-1304-2 |
| dewey-full |
610 |
| title_sort |
tie2 as a novel key factor of microangiopathy in systemic sclerosis |
| title_auth |
Tie2 as a novel key factor of microangiopathy in systemic sclerosis |
| abstract |
Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. |
| abstractGer |
Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. |
| abstract_unstemmed |
Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_OLC SSG-OLC-NED SSG-OLC-PHA SSG-OLC-DE-84 |
| title_short |
Tie2 as a novel key factor of microangiopathy in systemic sclerosis |
| url |
http://dx.doi.org/10.1186/s13075-017-1304-2 https://search.proquest.com/docview/1906361809 |
| remote_bool |
false |
| author2 |
Janine Schniering Jorg H W Distler Renate E Gay Steffen Gay Oliver Distler Britta Maurer |
| author2Str |
Janine Schniering Jorg H W Distler Renate E Gay Steffen Gay Oliver Distler Britta Maurer |
| ppnlink |
363765530 |
| mediatype_str_mv |
n |
| isOA_txt |
false |
| hochschulschrift_bool |
false |
| author2_role |
oth oth oth oth oth oth |
| doi_str |
10.1186/s13075-017-1304-2 |
| up_date |
2024-07-03T21:45:35.143Z |
| _version_ |
1803595950480949248 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a2200265 4500</leader><controlfield tag="001">OLC1995453560</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230515114337.0</controlfield><controlfield tag="007">tu</controlfield><controlfield tag="008">170721s2017 xx ||||| 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s13075-017-1304-2</subfield><subfield code="2">doi</subfield></datafield><datafield tag="028" ind1="5" ind2="2"><subfield code="a">PQ20170901</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)OLC1995453560</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)GBVOLC1995453560</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(PRQ)p642-71490e4dd5eeb1b65e8ec138cf6a05a7bb14266ca68b61b1308b4466b37865b93</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(KEY)0427448220170000019000000000tie2asanovelkeyfactorofmicroangiopathyinsystemicsc</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">DNB</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Falk Moritz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Tie2 as a novel key factor of microangiopathy in systemic sclerosis</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">ohne Hilfsmittel zu benutzen</subfield><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Band</subfield><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background The angiopoietin(Ang)/Tie2 system is a key regulator of vascular biology. The expression of membrane bound (mb) Tie2 and Ang-1 ensures vessel stability, whereas Ang-2, inducible by vascular endothelial growth factor (VEGF), hypoxia, and inflammation, acts as an antagonist. Tie2 signalling is also attenuated by soluble Tie2 (sTie2), the extracellular domain of the receptor, which is shed upon stimulation with VEGF. Herein, we investigate the role of Ang/Tie2 in the peripheral vasculopathy in systemic sclerosis (SSc) including animal models. Methods The expression of Ang-1/-2 and Tie2 in skin/serum of SSc patients was compared with healthy controls by immunohistochemistry (IHC)/ELISA. Expression of Ang/Tie2 was analysed in different animal models: VEGF transgenic (tg) mice, hypoxia model, bleomycin-induced skin fibrosis, and tight skin 1 (TSK1) mice. Results In SSc, dermal microvessels abundantly expressed Ang-2, but not Ang-1 compared with healthy controls. The percentage of mbTie2+ microvessels was profoundly decreased whereas the levels of sTie2 were increased already in early disease. Both in skin and sera of SSc patients, the Ang1/2 ratio was reduced, being lowest in patients with digital ulcers indicating vessel destabilizing conditions. We next studied potential influencing factors in animal models. The VEGF tg mouse model, the hypoxia, and the inflammation-dependent bleomycin model all showed a similar dysregulation of Ang/Tie2 as in SSc, which did not apply for the non-inflammatory TSK1 model. Conclusion Peripheral microvasculopathy in SSc results from a complex dysregulation of angiogenic signalling networks including the VEGF and the Ang/Tie2 system. The profoundly disturbed Ang-/Tie-2 balance might represent an important target for vascular therapeutic approaches in SSc.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Vascular endothelial growth factor</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rodents</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Extracellular matrix</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Arthritis</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hypoxia</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Janine Schniering</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jorg H W Distler</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Renate E Gay</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Steffen Gay</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Oliver Distler</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Britta Maurer</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Arthritis research & therapy</subfield><subfield code="d">London : BioMed Central, 2003</subfield><subfield code="g">19(2017)</subfield><subfield code="w">(DE-627)363765530</subfield><subfield code="w">(DE-600)2107602-9</subfield><subfield code="w">(DE-576)379407604</subfield><subfield code="x">1478-6354</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:19</subfield><subfield code="g">year:2017</subfield></datafield><datafield tag="856" ind1="4" ind2="1"><subfield code="u">http://dx.doi.org/10.1186/s13075-017-1304-2</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://search.proquest.com/docview/1906361809</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_OLC</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-NED</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-PHA</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SSG-OLC-DE-84</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">19</subfield><subfield code="j">2017</subfield></datafield></record></collection>
|
| score |
7.399349 |